L-lysine potentiates aminoglycosides against Acinetobacter baumannii via regulation of proton motive force and antibiotics uptake
L-lysine potentiates aminoglycosides against Acinetobacter baumannii via regulation of proton motive force and antibiotics uptake
复制标题
L-赖氨酸通过调节质子动力和抗生素摄取增强氨基糖苷类药物对抗鲍曼不动杆菌的作用
DOI：
10.1080/22221751.2020.1740611
复制
发表时间：
2020-01-01
影响因子：
13.2
通讯作者：
Long, Quanxin
中科院分区：
文献类型：
--
作者：
Deng, Wanyan;Fu, Tiwei;Long, Quanxin
摘要鲍曼不动杆菌是一种革兰氏阴性条件致病菌，是医院和社区获得性感染的主要原因。鲍曼不动杆菌可以迅速获得不同的耐药机制，并经历遗传修饰，从而对目前使用的所有临床抗生素产生耐药性和持久性。在这项研究中，我们发现外源性L-赖氨酸敏感鲍曼不动杆菌，其他革兰氏阴性菌（大肠杆菌和肺炎克雷伯菌）和革兰氏阳性菌（耻垢分枝杆菌）氨基糖苷类。重要的是，L-赖氨酸与氨基糖苷类的组合杀死了临床分离的多重耐药鲍曼不动杆菌和持久细胞。外源性L-赖氨酸可通过跨膜化学梯度增加质子动力，导致氨基糖苷类的积累，进一步解释活性氧的产生。L-赖氨酸和抗生素的组合突出了对抗细菌感染的有希望的策略。
ABSTRACT Acinetobacter baumannii, a Gram-negative opportunistic pathogen, is a leading cause of hospital- and community-acquired infections. Acinetobacter baumannii can rapidly acquire diverse resistance mechanisms and undergo genetic modifications that confer resistance and persistence to all currently used clinical antibiotics. In this study, we found exogenous L-lysine sensitizes Acinetobacter baumannii, other Gram-negative bacteria (Escherichia coli and Klebsiella pneumoniae) and a Gram-positive bacterium (Mycobacterium smegmatis) to aminoglycosides. Importantly, the combination of L-lysine with aminoglycosides killed clinically isolated multidrug-resistant Acinetobacter baumannii and persister cells. The exogenous L-lysine can increase proton motive force via transmembrane chemical gradient, resulting in aminoglycoside acumination that further accounts for reactive oxygen species production. The combination of L-lysine and antibiotics highlights a promising strategy against bacterial infection.